Virtual clinical trial simulations for a novel KRAS^G12C inhibitor (ASP2453) in non-small cell lung cancer.

ABSTRACT: KRAS is a small GTPase family protein that relays extracellular growth signals to cell nucleus. KRAS^G12C mutations lead to constitutive proliferation signaling and are prevalent across human cancers. ASP2453 is a novel, highly potent, and selective inhibitor of KRAS^G12C . Although preclinical data suggested impressive efficacy, it remains unclear whether ASP2453 will show more favorable clinical response compared to more advanced competitors, such as AMG 510. Here, we developed a quantitative systems pharmacology (QSP) model linking KRAS signaling to tumor growth in patients with non-small cell lung cancer. The model was parameterized using in vitro ERK1/2 phosphorylation and in vivo xenograft data for ASP2453. Publicly disclosed clinical data for AMG 510 were used to

SUBMITTER: Sayama H 

PROVIDER: S-EPMC8376128 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature